偏苯三酸酐诱导职业性哮喘大鼠模型的研究

Study on occupational asthma model rats induced by tri-meilitic-anhydride

目的以低分子量化工原料偏苯三酸酐（trimellitic—anhydride，TMA）作为致敏剂复制职业性哮喘大鼠模型。方法采用大鼠背部皮内注射致敏剂致敏，超声雾化器雾化吸人致敏剂激发的方法复制职业性哮喘大鼠模型，以大鼠引喘潜伏期，血液和支气管肺泡灌洗液（bronehoalveolarlavagefluid，BALF）中细胞学检查、BALF中IL-4和INF-y检测、血清IgE检测、大鼠离体气管条对乙酰胆碱的反应性、肺组织病理学检查为评判指标，考察TMA复制职业性哮喘大鼠模型的可行性。结果TMA模型组引喘潜伏期较短（与正常对照组比较Pd0．05），血液及BALF中嗜酸粒细胞（eosinophil，EOS）百分比升高（与正常对照组比较P〈0．05），血清中IgE升高（与正常对照组比较P〈0．05），BAI．F中IL-4升高、INF-γ降低（与正常对照组比较P〈0．05～0．01），模型组离体气管条对乙酰胆碱的反应性提高（与正常对照组比较P〈O．01），肺组织病理检查见肺支气管上皮细胞变性坏死脱落，支气管腔内可见大量EOS、单核细胞、淋巴细胞等炎性渗出物，以及管壁增厚、管腔狭窄等炎症表现。结论通过行为学观察、血液和BALF中细胞学检查、血清IgE检测、BALF中细胞因子检测和肺组织病理检测可见TMA致大鼠哮喘模型具有职业性哮喘的主要特征，表明采用TMA作为造模剂，适当的剂量和致敏方法复制类似职业性哮喘动物模型是可行的。

Objective To establish occupational asthma model by using tri-mellitic anhydride （ TMA ）, the low molecular weight industrial chemical, as sensitizer. Methods TMA was intracutaneously injected into subcutaneous of the back of rats, and aerosol inhalation for stimulation by ultrasonic nebulizer was applied. Incubation period of asthma, results of cyolgical examination of blood and bronchoalveolar lavage fluid （BALF）, contents of IL-4. INF-＇/ in BALF, and contents of IgE in serum, response of isolated trachea of rats to acetyl choline, pathological results of lung tissue were taken as the indexes to observe the viability of the replication. Results Incubation period of TMA model group was short （compared with control group, P d0.05） ; its percentage of eosinophilic granulocyte （EOS） in bronchoalveolar and blood lavage increased （compared with control group, P d0.05） ; its contents of lgE rose （compared with control group, P 〈0.05）. Contents of IL-4 in BALF rose, while INF contents of declined （compared with control group, P 〈0.05）. Response of isolated trachea of rats to acetyl choline of model group improved （compared with control group, P 〈0.01）. Moreover, degeneration, necrosis, and exfoliation of bronchial epithelial cells were detected in pathological examinatiom large amount of inflammatory effusion like eosnophils, monocytes and lymphocytes were found in the cavity of bronchus;inflammation expressions such as bronchial wall thickening and stenosis of bronchial cavity also appeared. Conclusions The indexing results exhibit the main features of occupational asthma in the model induced by TMA~ therefore, as the modeling agent, TMA is possible to be utilized by following proper dose and sensitizing methods to establish other similar clinical occupational asthma models.